chr15-32684900-A-G

Position:

• chr15-32684900-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001144757.3(SCG5):​c.489+231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,070 control chromosomes in the GnomAD database, including 28,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28286 hom., cov: 32)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67

Genes affected

SCG5 (HGNC:10816): (secretogranin V) This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-32684900-A-G is Benign according to our data. Variant chr15-32684900-A-G is described in ClinVar as [Benign]. Clinvar id is 1235123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.489+231A>G		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1728+231A>G		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.489+231A>G		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92349 AN: 151950 Hom.: 28264 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.608 AC: 92407 AN: 152070 Hom.: 28286 Cov.: 32 AF XY: 0.609 AC XY: 45286 AN XY: 74334

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.620

Alfa AF: 0.628 Hom.: 19849

Bravo AF: 0.597

Asia WGS AF: 0.637 AC: 2213 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0050
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7165737; hg19: chr15-32977101;